Evidence map›Paper›PMID 31915244›Full record

ArticleThe Journal of biological chemistry2020

A genome-wide analysis of targets of macrolide antibiotics in mammalian cells.

Amita Gupta, Aye Ökesli-Armlovich, David Morgens, Michael C Bassik, Chaitan Khosla

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.7field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 16 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Amita GuptaDepartment of Chemical Engineering, Stanford University, Stanford, California 94305; Stanford Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, California 94305.
Aye Ökesli-ArmlovichStanford Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, California 94305; Department of Chemistry, Stanford University, Stanford, California 94305.
David MorgensDepartment of Genetics, Stanford University, Stanford, California 94305.
Michael C BassikStanford Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, California 94305; Department of Genetics, Stanford University, Stanford, California 94305.
Chaitan KhoslaDepartment of Chemical Engineering, Stanford University, Stanford, California 94305; Stanford Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, California 94305; Department of Chemistry, Stanford University, Stanford, California 94305; Department of Biochemistry, Stanford University, Stanford, California 94305. Electronic address: khosla@stanford.edu.
Stanford Health Care · USStanford University · US

Funding

Translational Incubator CoreU19AI109662 · NIAID · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2014 to 2019
$28.6M
Structure, Mechanism, and Engineering of Assembly Line Polyketide SynthasesR01GM087934 · NIGMS · STANFORD UNIVERSITY · PI KHOSLA, CHAITAN · 2009 to 2021
$4.9M
Accelerating drug development and repurposing using systematic genetic interactioDP2HD084069 · NICHD · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C · 2014 to 2014
$2.4M
NIAID NIH HHS U19 AI109662NICHD NIH HHS DP2 HD084069NIGMS NIH HHS R01 GM087934
6 · The paper itself

Abstract

Macrolide antibiotics, such as erythromycin and josamycin, are natural polyketide products harboring 14- to 16-membered macrocyclic lactone rings to which various sugars are attached. These antibiotics are used extensively in the clinic because of their ability to inhibit bacterial protein synthesis. More recently, some macrolides have been shown to also possess anti-inflammatory and other therapeutic activities in mammalian cells. To better understand the targets and effects of this drug class in mammalian cells, we used a genome-wide shRNA screen in K562 cancer cells to identify genes that modulate cellular sensitivity to josamycin. Among the most sensitizing hits were proteins involved in mitochondrial translation and the mitochondrial unfolded protein response, glycolysis, and the mitogen-activated protein kinase signaling cascade. Further analysis revealed that cells treated with josamycin or other antibacterial agents exhibited impaired oxidative phosphorylation and metabolic shifts to glycolysis. Interestingly, we observed that knockdown of the mitogen-activated protein kinase kinase kinase 4 (

Indexed as

AnimalsAnti-Bacterial AgentsDrug Resistance, MicrobialErythromycinGene Expression RegulationGlycolysisHumansJosamycinK562 CellsMacrolidesMAP Kinase Kinase Kinase 4MAP Kinase Signaling SystemMitogen-Activated Protein KinasesOxidative Phosphorylationp38 Mitogen-Activated Protein KinasesProtein BiosynthesisAnti-Bacterial AgentsErythromycinJosamycinMacrolidesMAP3K4 protein, humanMAP Kinase Kinase Kinase 4Mitogen-Activated Protein Kinasesp38 Mitogen-Activated Protein KinasesProtein Synthesis Inhibitorsantibioticsdrug actionerythromycinjosamycinmitochondriamitochondrial translationnatural productshRNA

Identifiers

PMID31915244
PMCPMC7029112
OpenAlexW3000271207

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.